ES2349754T3 - Andrógenos novedosos. - Google Patents
Andrógenos novedosos. Download PDFInfo
- Publication number
- ES2349754T3 ES2349754T3 ES05737941T ES05737941T ES2349754T3 ES 2349754 T3 ES2349754 T3 ES 2349754T3 ES 05737941 T ES05737941 T ES 05737941T ES 05737941 T ES05737941 T ES 05737941T ES 2349754 T3 ES2349754 T3 ES 2349754T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- nitro
- cyano
- indole
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000003098 androgen Substances 0.000 title description 14
- 229940030486 androgens Drugs 0.000 title description 8
- -1 cyano, formyl Chemical group 0.000 claims abstract description 174
- 150000001875 compounds Chemical class 0.000 claims abstract description 150
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 99
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 36
- 239000001257 hydrogen Substances 0.000 claims abstract description 35
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 33
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 29
- 150000002367 halogens Chemical class 0.000 claims abstract description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 26
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 26
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 22
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 12
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 7
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 7
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims abstract description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract 2
- 239000000460 chlorine Substances 0.000 claims description 33
- 229910052801 chlorine Inorganic materials 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 125000006288 3,5-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(C([H])=C1F)C([H])([H])* 0.000 claims description 28
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 25
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 22
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- 239000011737 fluorine Substances 0.000 claims description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 16
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- RRRBPKKMUGCKTD-UHFFFAOYSA-N 1-[(3,5-difluorophenyl)methyl]-n-methyl-3-(2-nitrophenyl)sulfanylindol-6-amine Chemical compound C=1N(CC=2C=C(F)C=C(F)C=2)C2=CC(NC)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O RRRBPKKMUGCKTD-UHFFFAOYSA-N 0.000 claims description 5
- BSXCJNDVWKVFSF-UHFFFAOYSA-N 2-[1-[(3,5-difluorophenyl)methyl]-6-(methylamino)indol-3-yl]sulfanylbenzonitrile Chemical compound C=1N(CC=2C=C(F)C=C(F)C=2)C2=CC(NC)=CC=C2C=1SC1=CC=CC=C1C#N BSXCJNDVWKVFSF-UHFFFAOYSA-N 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 4
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical group COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims description 4
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims description 4
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- KGNITIORKHRLEL-UHFFFAOYSA-N 1-(furan-2-ylmethyl)-n-methyl-3-(2-nitrophenyl)sulfanylindol-6-amine Chemical compound C=1N(CC=2OC=CC=2)C2=CC(NC)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O KGNITIORKHRLEL-UHFFFAOYSA-N 0.000 claims description 3
- BHXJZJBFHFJSJP-UHFFFAOYSA-N 1-[(3,5-difluorophenyl)methyl]-n-(2-methoxyethyl)-3-(2-nitrophenyl)sulfanylindol-6-amine Chemical compound C=1N(CC=2C=C(F)C=C(F)C=2)C2=CC(NCCOC)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O BHXJZJBFHFJSJP-UHFFFAOYSA-N 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 239000002583 male contraceptive agent Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- PZRKAAVAWINWBI-UHFFFAOYSA-N n-methyl-3-(2-nitrophenyl)sulfanyl-1-(pyridin-3-ylmethyl)indol-6-amine Chemical compound C=1N(CC=2C=NC=CC=2)C2=CC(NC)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O PZRKAAVAWINWBI-UHFFFAOYSA-N 0.000 claims description 3
- HCFFYOWYOSJBMJ-UHFFFAOYSA-N 1-(furan-3-ylmethyl)-n-methyl-3-(2-nitrophenyl)sulfanylindol-6-amine Chemical compound C=1N(CC2=COC=C2)C2=CC(NC)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O HCFFYOWYOSJBMJ-UHFFFAOYSA-N 0.000 claims description 2
- QBGKDQIZNDJGFH-UHFFFAOYSA-N 1-[[1-[(3,5-difluorophenyl)methyl]-3-(2-nitrophenyl)sulfanylindol-6-yl]amino]propan-2-one Chemical compound C=1N(CC=2C=C(F)C=C(F)C=2)C2=CC(NCC(=O)C)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O QBGKDQIZNDJGFH-UHFFFAOYSA-N 0.000 claims description 2
- MQWIOFLGUYHMNX-UHFFFAOYSA-N 2-[[1-[(3,5-difluorophenyl)methyl]-3-(2-nitrophenyl)sulfanylindol-6-yl]amino]ethanol Chemical compound C=1N(CC=2C=C(F)C=C(F)C=2)C2=CC(NCCO)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O MQWIOFLGUYHMNX-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 267
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 126
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 110
- 239000000047 product Substances 0.000 description 98
- 238000000034 method Methods 0.000 description 96
- 238000005160 1H NMR spectroscopy Methods 0.000 description 63
- 238000004440 column chromatography Methods 0.000 description 62
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 230000002829 reductive effect Effects 0.000 description 47
- 239000000243 solution Substances 0.000 description 47
- 239000000203 mixture Substances 0.000 description 40
- 239000011541 reaction mixture Substances 0.000 description 39
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 37
- 229910052938 sodium sulfate Inorganic materials 0.000 description 37
- 235000011152 sodium sulphate Nutrition 0.000 description 37
- 239000012267 brine Substances 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
- 239000012074 organic phase Substances 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- 239000007864 aqueous solution Substances 0.000 description 29
- 229920006395 saturated elastomer Polymers 0.000 description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 239000002585 base Substances 0.000 description 24
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 22
- 239000004215 Carbon black (E152) Substances 0.000 description 21
- 229930195733 hydrocarbon Natural products 0.000 description 21
- 239000011734 sodium Substances 0.000 description 21
- 229910052708 sodium Inorganic materials 0.000 description 21
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 17
- 238000011282 treatment Methods 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 108010080146 androgen receptors Proteins 0.000 description 15
- 102000005962 receptors Human genes 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- 102000001307 androgen receptors Human genes 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 239000002168 alkylating agent Substances 0.000 description 12
- 229940100198 alkylating agent Drugs 0.000 description 12
- 238000005804 alkylation reaction Methods 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- HKEIRTILOAZJBN-UHFFFAOYSA-N 1-[(3,5-difluorophenyl)methyl]-3-(2-nitrophenyl)sulfanylindol-6-amine Chemical compound C=1N(CC=2C=C(F)C=C(F)C=2)C2=CC(N)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O HKEIRTILOAZJBN-UHFFFAOYSA-N 0.000 description 11
- 230000029936 alkylation Effects 0.000 description 11
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 11
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 235000019270 ammonium chloride Nutrition 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- PSWCIARYGITEOY-UHFFFAOYSA-N 6-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2C=CNC2=C1 PSWCIARYGITEOY-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 230000001548 androgenic effect Effects 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- 238000007126 N-alkylation reaction Methods 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 229940088597 hormone Drugs 0.000 description 6
- 239000005556 hormone Substances 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 6
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
- GDPMYFJTTCDOBI-UHFFFAOYSA-N 3-(2-nitrophenyl)sulfanyl-1-(pyridin-2-ylmethyl)indol-6-amine Chemical compound C=1N(CC=2N=CC=CC=2)C2=CC(N)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O GDPMYFJTTCDOBI-UHFFFAOYSA-N 0.000 description 5
- CRZYRTKBXWBJLC-UHFFFAOYSA-N 3-(2-nitrophenyl)sulfanyl-1-(pyridin-3-ylmethyl)indol-6-amine Chemical compound C=1N(CC=2C=NC=CC=2)C2=CC(N)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O CRZYRTKBXWBJLC-UHFFFAOYSA-N 0.000 description 5
- 241000282414 Homo sapiens Species 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 230000003637 steroidlike Effects 0.000 description 5
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 5
- VOZUAUHDHXKHCR-UHFFFAOYSA-N tert-butyl n-methyl-n-[3-(2-nitrophenyl)sulfanyl-1h-indol-6-yl]carbamate Chemical compound C=1NC2=CC(N(C(=O)OC(C)(C)C)C)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O VOZUAUHDHXKHCR-UHFFFAOYSA-N 0.000 description 5
- REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 4
- 101100232079 Arabidopsis thaliana HSR4 gene Proteins 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 4
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 150000002475 indoles Chemical class 0.000 description 4
- ZNYRFQLLMACTIT-UHFFFAOYSA-N n-methyl-3-(2-nitrophenyl)sulfanyl-1-(pyridin-2-ylmethyl)indol-6-amine Chemical compound C=1N(CC=2N=CC=CC=2)C2=CC(NC)=CC=C2C=1SC1=CC=CC=C1[N+]([O-])=O ZNYRFQLLMACTIT-UHFFFAOYSA-N 0.000 description 4
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 239000000583 progesterone congener Substances 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 4
- NTNKNFHIAFDCSJ-UHFFFAOYSA-N (2-nitrophenyl) thiohypochlorite Chemical compound [O-][N+](=O)C1=CC=CC=C1SCl NTNKNFHIAFDCSJ-UHFFFAOYSA-N 0.000 description 3
- GDRLBZVQBUEONM-UHFFFAOYSA-N 2-[6-amino-1-(pyridin-2-ylmethyl)indol-3-yl]sulfanylbenzonitrile Chemical compound C=1N(CC=2N=CC=CC=2)C2=CC(N)=CC=C2C=1SC1=CC=CC=C1C#N GDRLBZVQBUEONM-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Reproductive Health (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Pregnancy & Childbirth (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Gynecology & Obstetrics (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04101700 | 2004-04-23 | ||
| EP04101700 | 2004-04-23 | ||
| US565043P | 2004-04-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2349754T3 true ES2349754T3 (es) | 2011-01-11 |
Family
ID=34929000
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES05737941T Expired - Lifetime ES2349754T3 (es) | 2004-04-23 | 2005-04-21 | Andrógenos novedosos. |
Country Status (17)
| Country | Link |
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| US (2) | US7812036B2 (enExample) |
| EP (1) | EP1742912B1 (enExample) |
| JP (1) | JP4997101B2 (enExample) |
| CN (1) | CN1956954B (enExample) |
| AR (1) | AR049885A1 (enExample) |
| AT (1) | ATE478844T1 (enExample) |
| AU (1) | AU2005235751B2 (enExample) |
| BR (1) | BRPI0510078A (enExample) |
| CA (1) | CA2562571C (enExample) |
| DE (1) | DE602005023145D1 (enExample) |
| ES (1) | ES2349754T3 (enExample) |
| IL (1) | IL178562A (enExample) |
| MX (1) | MXPA06012201A (enExample) |
| MY (1) | MY144304A (enExample) |
| PE (1) | PE20060196A1 (enExample) |
| TW (1) | TW200602317A (enExample) |
| WO (1) | WO2005102998A1 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20050396A2 (en) | 2002-11-07 | 2005-06-30 | Akzo Nobel N.V. | Indoles useful in the treatment of androgen-receptor related diseases |
| BRPI0907844B8 (pt) | 2008-02-22 | 2021-05-25 | Radius Health Inc | compostos e método para modular um receptor de andrógeno, processos de preparação e composição farmacêutica dos mesmos e seus usos |
| US8268872B2 (en) | 2008-02-22 | 2012-09-18 | Radius Health, Inc. | Selective androgen receptor modulators |
| US8987319B2 (en) | 2010-02-04 | 2015-03-24 | Radius Health, Inc. | Selective androgen receptor modulators |
| PT2568806T (pt) | 2010-05-12 | 2016-08-05 | Radius Health Inc | Regimes terapêuticos |
| US8642632B2 (en) | 2010-07-02 | 2014-02-04 | Radius Health, Inc. | Selective androgen receptor modulators |
| WO2012047617A1 (en) | 2010-09-28 | 2012-04-12 | Radius Health, Inc. | Selective androgen receptor modulators |
| PL3122426T3 (pl) | 2014-03-28 | 2023-05-15 | Duke University | Leczenie raka sutka z zastosowaniem selektywnych modulatorów receptora estrogenowego |
| US9421264B2 (en) | 2014-03-28 | 2016-08-23 | Duke University | Method of treating cancer using selective estrogen receptor modulators |
| SMT202200199T1 (it) | 2016-06-22 | 2022-07-21 | Ellipses Pharma Ltd | Metodi di trattamento del cancro del seno ar+. |
| EP4374925A3 (en) | 2017-01-05 | 2025-01-15 | Radius Pharmaceuticals, Inc. | Polymorphic forms of rad1901-2hcl |
| CN112423844B (zh) | 2018-07-04 | 2024-08-13 | 雷迪厄斯制药公司 | Rad1901-2hcl的多晶型形式 |
| CN119390714A (zh) | 2019-02-12 | 2025-02-07 | 雷迪厄斯制药公司 | 方法和化合物 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
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| NZ179580A (en) | 1974-12-30 | 1978-04-03 | Mcneilab Inc | 2-or 3-(w-tertiaryaminoalkyl)-thioindoles and the corresponding sulfinyl and sulfonyl analogs |
| US4059583A (en) * | 1975-11-13 | 1977-11-22 | Mcneil Laboratories, Incorporated | Substituted indoles |
| JPS63313770A (ja) | 1987-06-16 | 1988-12-21 | Sumitomo Chem Co Ltd | イサチン誘導体、その製造法およびそれを有効成分とする除草剤 |
| ES2054784T3 (es) | 1987-08-08 | 1994-08-16 | Akzo Nv | Un metodo para la fabricacion de un implante. |
| DE3924052A1 (de) | 1989-07-21 | 1991-01-24 | Bayer Ag | N- (indol-6-yl)-heterocyclen |
| FR2662713B1 (fr) * | 1990-05-29 | 1994-04-08 | Oreal | Procede de teinture de fibres keratiniques avec un aminoindole associe a un derive quinonique. |
| FR2675380A1 (fr) | 1991-04-18 | 1992-10-23 | Oreal | Procede de teinture des fibres keratiniques avec des aminoindoles, a ph basique, compositions mises en óoeuvre et nouveaux composes. |
| US5938792A (en) * | 1991-04-18 | 1999-08-17 | L'oreal | Process for dyeing keratinous fibers with aminoindoles and oxidation dye precursors at basic Ph's and dyeing agents |
| GB9204365D0 (en) | 1992-02-28 | 1992-04-08 | Pfizer Ltd | Indoles |
| US5482960A (en) | 1994-11-14 | 1996-01-09 | Warner-Lambert Company | Nonpeptide endothelin antagonists |
| JP3107290B2 (ja) * | 1996-05-20 | 2000-11-06 | 株式会社日立製作所 | 燃料装荷方法 |
| HUP9904215A3 (en) | 1996-11-25 | 2002-01-28 | Procter & Gamble | 2-imidazolinylaminoindole compounds useful as alpha-2 adrenoceptor agonists |
| TW358031B (en) | 1997-04-11 | 1999-05-11 | Akze Nobel N V | Drug delivery system for 2 or more active substances |
| US5969155A (en) * | 1997-04-11 | 1999-10-19 | The United States Of America As Represented By The Secretary Of The Army | Conversion of trinitrotoluene into high value compounds |
| HUP0100156A3 (en) | 1998-02-25 | 2002-12-28 | Genetics Inst Inc Cambridge | Indole derivatives as inhibitors of phospholipase a2 and use of them for producing pharmaceutical compositions |
| JP2002504539A (ja) | 1998-02-25 | 2002-02-12 | ジェネティックス・インスチチュート・インコーポレーテッド | ホスホリパーゼ酵素の阻害剤 |
| GB9819033D0 (en) | 1998-09-01 | 1998-10-28 | Cerebrus Ltd | Chemical compounds VI |
| US6645974B2 (en) | 2001-07-31 | 2003-11-11 | Merck & Co., Inc. | Androgen receptor modulators and methods for use thereof |
| US6933316B2 (en) * | 2001-12-13 | 2005-08-23 | National Health Research Institutes | Indole compounds |
| JP4316232B2 (ja) * | 2001-12-28 | 2009-08-19 | 武田薬品工業株式会社 | アンドロゲン受容体拮抗剤 |
| AU2002367424A1 (en) | 2001-12-28 | 2003-07-24 | Takeda Chemical Industries, Ltd. | Androgen receptor antagonists |
| PL373410A1 (en) * | 2002-02-01 | 2005-08-22 | F.Hoffman-La Roche Ag | Substituted indoles as alpha-1 agonists |
| UA79504C2 (en) * | 2002-11-07 | 2007-06-25 | Organon Nv | Indols for treating diseases associated with androgen receptors |
| HRP20050396A2 (en) * | 2002-11-07 | 2005-06-30 | Akzo Nobel N.V. | Indoles useful in the treatment of androgen-receptor related diseases |
| RU2313524C2 (ru) * | 2003-05-09 | 2007-12-27 | Ф.Хоффманн-Ля Рош Аг | МИТИЛИНДОЛЫ И МЕТИЛПИРРОЛОПИРИДИНЫ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ОБЛАДАЮЩАЯ АКТИВНОСТЬЮ α-1-АДРЕНЕРГИЧЕСКИХ АГОНИСТОВ |
-
2005
- 2005-04-13 TW TW094111712A patent/TW200602317A/zh unknown
- 2005-04-21 PE PE2005000446A patent/PE20060196A1/es not_active Application Discontinuation
- 2005-04-21 JP JP2007508908A patent/JP4997101B2/ja not_active Expired - Fee Related
- 2005-04-21 US US11/587,192 patent/US7812036B2/en not_active Expired - Fee Related
- 2005-04-21 EP EP05737941A patent/EP1742912B1/en not_active Expired - Lifetime
- 2005-04-21 CN CN2005800164068A patent/CN1956954B/zh not_active Expired - Fee Related
- 2005-04-21 BR BRPI0510078-0A patent/BRPI0510078A/pt not_active IP Right Cessation
- 2005-04-21 MX MXPA06012201A patent/MXPA06012201A/es active IP Right Grant
- 2005-04-21 DE DE602005023145T patent/DE602005023145D1/de not_active Expired - Lifetime
- 2005-04-21 ES ES05737941T patent/ES2349754T3/es not_active Expired - Lifetime
- 2005-04-21 WO PCT/EP2005/051766 patent/WO2005102998A1/en not_active Ceased
- 2005-04-21 CA CA2562571A patent/CA2562571C/en not_active Expired - Fee Related
- 2005-04-21 AU AU2005235751A patent/AU2005235751B2/en not_active Ceased
- 2005-04-21 AT AT05737941T patent/ATE478844T1/de not_active IP Right Cessation
- 2005-04-22 MY MYPI20051785A patent/MY144304A/en unknown
- 2005-04-22 AR ARP050101602A patent/AR049885A1/es unknown
-
2006
- 2006-10-15 IL IL178562A patent/IL178562A/en not_active IP Right Cessation
-
2010
- 2010-09-22 US US12/887,607 patent/US20110009428A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AR049885A1 (es) | 2006-09-13 |
| CN1956954A (zh) | 2007-05-02 |
| CA2562571C (en) | 2013-01-08 |
| AU2005235751A1 (en) | 2005-11-03 |
| JP4997101B2 (ja) | 2012-08-08 |
| EP1742912B1 (en) | 2010-08-25 |
| MY144304A (en) | 2011-08-29 |
| PE20060196A1 (es) | 2006-04-01 |
| IL178562A (en) | 2011-05-31 |
| WO2005102998A1 (en) | 2005-11-03 |
| AU2005235751B2 (en) | 2011-03-24 |
| CA2562571A1 (en) | 2005-11-03 |
| US20070225352A1 (en) | 2007-09-27 |
| IL178562A0 (en) | 2007-02-11 |
| DE602005023145D1 (de) | 2010-10-07 |
| BRPI0510078A (pt) | 2007-10-16 |
| US20110009428A1 (en) | 2011-01-13 |
| EP1742912A1 (en) | 2007-01-17 |
| ATE478844T1 (de) | 2010-09-15 |
| MXPA06012201A (es) | 2007-01-17 |
| JP2007533707A (ja) | 2007-11-22 |
| US7812036B2 (en) | 2010-10-12 |
| CN1956954B (zh) | 2011-05-04 |
| TW200602317A (en) | 2006-01-16 |
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